Drug Interaction Report

Coadministration with inhibitors of CYP450 2C9 may increase the serum levels and effects of carvedilol. The mechanism is inhibition of CYP450 2C9, one of the primary isoenzymes involved in the metabolism of carvedilol. According to the prescribing information, CYP450 2C9 is thought to be of importance in the O-methylation pathway of S(-)-carvedilol. Further reductions in heart rate or cardiac conduction may occur.

MONITOR: Two cases have been reported in which patients on sulfamethoxazole-trimethoprim therapy, after consuming beer, reported flushing, heart palpitations, dyspnea, headache, and nausea (disulfiram - alcohol type reactions). First-generation sulfonylureas have been reported to cause facial flushing when administered with alcohol by inhibiting acetaldehyde dehydrogenase and subsequently causing acetaldehyde accumulation. Since sulfamethoxazole is chemically related to first-generation sulfonylureas, a disulfiram-like reaction with products containing sulfamethoxazole is theoretically possible. However, pharmacokinetic/pharmacodynamic data are lacking and in addition, the two reported cases cannot be clearly attributed to the concomitant use of sulfamethoxazole-trimethoprim and alcohol.

MANAGEMENT: Patients should be alerted to the potential for this interaction and although the risk for this interaction is minimal, caution is recommended while taking sulfamethoxazole-trimethoprim concomitantly with alcohol.